: This amended application is designed to respond as completely as possible to concerns of the site visitors and of subsequent review groups. Accordingly, eight disciplinary Research Cores have been replaced by three multidisciplinary, integrated Research Cores. Facility Cores have been strengthened. The requirements and benefits of Center membership have been clarified. Leadership issues have been addressed. In toto, this program has been refocused and energized by these structural changes. Our Center fosters active collaborations among three Research Cores: 1) Metals, 2) Urban and Occupational Particles, and 3) Organic Pollutants. The work of the Research Cores is greatly enhanced by three Facility Cores: 1) Biological Analyses, 2) Exposures and Environmental Analyses, and 3) Environmental Statistics. Finally, the investigators'ability to make their research and knowledge available to the public is greatly enhanced by the Community Outreach and Education Program (COEP). Other Center activities, such as pilot projects, new investigators, and program enrichment are catalytic mechanisms to achieve integration, interaction, productive, and innovative science. The objectives of this NIEHS Center are to generate new knowledge relating to the physiology, pharmacology, pathology, cell biology, molecular biology, genetics, and epidemiology of environmental disease, and to apply this knowledge to new modalities of prevention, diagnosis, and therapy. The investigators achieve these objectives through a variety of approaches, which range from studies of molecules and cells to those of whole animals and human populations. Through the organizational structure and financial support provided by the NIEHS Center Grant, the investigators'will increase the impact of their research and teaching in environmental health. In toto, the Harvard NIEHS Center for Environmental Health continues to be a major focal point for environmental research and training in Boston. The NIEHS Center mechanism enhances connections and makes the Harvard NIEHS Center part of a national and international network.